My long-term goal is to become an established independent bio-behavioral epidemiologist and to design, implement and analyze studies that combine genetic and non-genetic influences on behaviors that effect cancer and other health outcomes. My proposal builds upon my previous training in community psychology and quantitative methods, and outlines further training in genetics, epidemiology and analytic techniques. I have developed a comprehensive education and mentoring plan that will provide intensive instruction in these areas. My research builds upon an ongoing R01 (R01 CA105203-01; Spitz PI) that determines the relative influences of non-genetic and genetic factors in experimenting with cigarettes and nicotine dependence in 1,300 Mexican-American youth in the Houston metropolitan area. I will extend and enrich the data from the parent grant by assessing behavioral aspects of acculturation, sensation-seeking tendencies, participation in physical activities, and by completing additional genotyping on DRD2, DRD4, and the dopamine transporter gene. I focus on these polymorphisms because they are associated with sensation seeking, physical activity and smoking behaviors. These additional data will permit novel assessments of the potential moderating and/or mediating influences that acculturation and PA have on the relationship between experimenting with cigarettes and underlying behavioral- and genetic-based variations in sensation seeking. I also will examine the role of nicotinic cholinergic receptor genes that have been identified to be important in nicotine dependence among other populations to confirm this relationship in Mexican Americans. Among the adolescent participants enrolled in the parent study, my specific aims are to: 1) assess the independent effects of acculturation (linguistic and behavioral aspects) and sensation-seeking tendencies on experimentation with cigarettes and level of physical activity; 2) determine if either acculturation or physical activity moderate the influence of sensation seeking on experimentation with cigarettes; and 3) explore how variants in selected candidate genes influence experimenting with cigarettes, physical activity, or both. The additional data collected in this K07 will enable me to focus on questions that can not currently be addressed in the parent R01, will lead to the generation of new hypotheses, and will enable a more thorough investigation of gene variants in the dopamine reward pathway. The additional data will be added to the data collected in the parent R01 to develop quantitative multivariate risk assessment models for psychosocial, contextual, and genetic susceptibility to identify high-risk adolescent subgroups. These findings will enable us in the longer term to develop more effective, culturally appropriate school- and community-based interventions to promote healthier lifestyles. Recently I have been recommended for promotion to Assistant Professor. I am confident that the net effect of the promotion and obtaining this fellowship will launch my career in cancer prevention.